Trauma, a major health problem results in significant alterations in pathophysiological mechanisms. Victims of trauma generally do not succumb from an altered endocrine or metabolic state but rather to sepsis, despite the use of antibiotics. Characteristically, immunologic incompetence develops rapidly after trauma. The relationships of altered hormones/ substrates to the etiology of trauma-induced anergy is not known. This project is designed to examine these hypotheses: (1) that changes in the hormone metabolic environment following trauma are responsible (in part) for loss of immunologic functions; (2) that experimental manipulations of the hormone environment may prevent depression of the immune system following trauma; (3) that due to trauma-induced changes in the hormonal/metabolic environment, circulating inhibitory factors (CIF) exist in anergy. A model of trauma (thermal injury) will be evaluated with respect to hormonal (ACTH, F, T4, T3, rT3, PGE2 catecholamine, insulin, glucagon) and metabolic (glucose, amino acids, free fatty acids) changes in the immunized guinea pig (IGP) following trauma. These changes will be correlated with the following parameters of immune function: (1) In vivok immediate hypersensitivity (IH) and delayed hypersensitivity reactions (DH); (2) In vitro lymphocyte blastogenic response to mitogens; (3) identification of the presence of CIF on DH and blast transformation (BT), restoration of BT with interleukins and (4) development of the "red line" phenomena; and (5) changes in mononuclear lymphocyte AA. The above endocrine and metabolic parameters will be examined at 24 hor, 1, 2 and 4 wk post trauma, as will IH and DH and its in vitro correlates. In order to (a) identify the hormones which are sufficient to induce anergy, those hormones found to increase following trauma will be chronically infused into nontraumatized (NT) IGP, and immune function assessed; (b) define the necessary hormonal sequelae of trauma-induced anergy, endocrine ablated IGP, and IGP infused with pharmacologic blockers of hormone synthesis/release will be studied; (c) identify CIF, recipient NTIGP will be injected with sera from dona anergic IGB. The results from these studies could suggest modifications of the hormonal/environment to influence the trauma victim's resistance to the onset of sepsis, thereby improving morbidity and reducing the risk of mortality following severe injury.